| Project/Area Number |
17590797
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Kumamoto University |
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Principal Investigator |
TAKAHASHI Kiyoshi (2006) Kumamoto University, Graduate School of Medical Sciences, Emeritus Professor (70045631)
寺崎 泰弘 (2005) 熊本大学, 大学院・医学薬学研究部, 助手 (50332870)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEYA Motohiro Kumamoto University, Graduate School of Medical Sciences, Professor (90155052)
AKAIKE Takaaki Kumamoto University, Graduate School of Medical Sciences, Professor (20231798)
高橋 潔 熊本大学, 大学院・医学薬学研究部, 名誉教授 (70045631)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | 8-nitoroguanosine / carcinogenesis / gene modification / pulmonary fibrosis / hyperoxia-induced lung injury / survival siganl / nucleic acid damage / animal model |
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| Research Abstract |
8-nitroguanosine, a modified base, draws people's attention as a marker for nucleic acid damage during carcinogenesis or other gene modification. Since we have succeeded in producing a specific antibody against 8-nitroguanosine, we studied the generation and localization of 8-nitroguanosine in various pulmonary diseases using the antibody.
In pulmonary fibrosis, strong immunostaining for 8-nitroguanosine was observed in metaplastic epithelial cells as well as macrophages and alveolar epithelia. Colocalization of 8-nitroguanosine with iNOS, eNOS, hemoxygenase-1, 8-nitotyrosine, and p53 was detected in confocal laser scanning microscopy. In lung cancer, 8-nitroguanosine is observed both in cytoplasm and nuclei of cancer cells. These results suggest that 8-nitroguanosin is involved in injury of air-space epithelia and also in pulmonary carcinogenesis. In lung injury mouse models induced by hyperoxia-exposure or bleomycin showed that 8-nitorguanosine is generated in air-space epitheial cells as well as in macrophages accumulated in injured tissue indicating that 8-nitroguanosine is involved in such disease processes.
We have previously shown that 8-nitro-cyclic GMP, a nitroguanosine derivative, activates cell survival by inducing hemoxigenase-1 and other cytoprotective molecules. It is considered that 8-nitoroguanosine is not a silent damaged base but a highly active molecule possessing signaling transmittal function.
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